Static secondary ion mass spectrometry to monitor solid-phase peptide synthesis

Insights into the direct monitoring of supported peptide synthesis were rea lized through the design of time of flight static secondary ion mass spectr ometry (TOF-S-SIMS) experiments. The mass spectrometric method was carried out at the resin bead level and was found reproducible (intra- and inter-da y assays), sensitive (femtomol level) and non-destructive (only 0.01% of th e peptides were destroyed by the primary ion beam bombardment). The nature of the peptide-resin linkage governed the recovery of ions characterizing t he whole peptide sequence. A S-SIMS cleavable bond was thus required solely in that position to achieve the release of the growing structures from the insoluble support into the gas phase without any fragmentation. Results ar e presented with standard solid-phase resins allowing linkage through an am ide or an ester bond. The latter was orthogonally broken upon the bombardme nt and thus constituted a convenient S-SIMS cleavable bond. (C) 2001 Americ an Society for Mass Spectrometry.